609
Views
22
CrossRef citations to date
0
Altmetric
Review

Prediction of response to methotrexate in rheumatoid arthritis

ORCID Icon, & ORCID Icon
Pages 419-429 | Received 01 Mar 2018, Accepted 12 Apr 2018, Published online: 26 Apr 2018

References

  • Haraoui B, Pope J. Treatment of early rheumatoid arthritis: concepts in management. Semin Arthritis Rheum. 2011 Apr;40(5):371–388. PubMed PMID: 21295822.
  • Mikkelsen TS, Thorn CF, Yang JJ, et al. PharmGKB summary: methotrexate pathway. Pharmacogenet Genomics. 2011 Oct;21(10):679–686. PubMed PMID: 21317831; PubMed Central PMCID: PMCPMC3139712.
  • Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis. 2009 Jul;68(7):1094–1099. PubMed PMID: 19033290; PubMed Central PMCID: PMCPMC2689521.
  • Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis. 2009 Jul;68(7):1100–1104. PubMed PMID: 19060002; PubMed Central PMCID: PMCPMC2689525.
  • Hyrich KL, Watson KD, Silman AJ, et al. British society for rheumatology biologics r. predictors of response to anti-tnf-alpha therapy among patients with rheumatoid arthritis: results from the british society for rheumatology biologics register. Rheumatology (Oxford, England). 2006 Dec;45(12):1558–1565. PubMed PMID: 16705046.
  • Farragher TM, Lunt M, Fu B, et al. Early treatment with, and time receiving, first disease-modifying antirheumatic drug predicts long-term function in patients with inflammatory polyarthritis. Ann Rheum Dis. 2010 Apr;69(4):689–695. PubMed PMID: 19858538; PubMed Central PMCID: PMCPMC2927614.
  • Ansari A, Hassan C, Duley J, et al. Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. Aliment Pharmacol Ther. 2002 Oct;16(10):1743–1750. PubMed PMID: 12269967.
  • Barsh GS, Copenhaver GP, Gibson G, et al. Guidelines for genome-wide association studies. PLoS Genetics. 2012 Jul;8(7):e1002812. PubMed PMID: 22792080; PubMed Central PMCID: PMC3390399. eng.
  • Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987 Nov;30(11):1205–1213. PubMed PMID: 2446635; eng
  • Mewar D, Marinou I, Coote AL, et al. Association between radiographic severity of rheumatoid arthritis and shared epitope alleles: differing mechanisms of susceptibility and protection. Ann Rheum Dis. 2008 Jul;67(7):980–983. PubMed PMID: 17901090; eng.
  • O’Dell JR, Nepom BS, Haire C, et al. HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments. Ann Rheum Dis. 1998 Apr;57(4):209–213. PubMed PMID: 9709176; PubMed Central PMCID: PMC1752573. eng.
  • Hider SL, Silman AJ, Thomson W, et al. Can clinical factors at presentation be used to predict outcome of treatment with methotrexate in patients with early inflammatory polyarthritis? [Research Support, Non-U.S. Gov’t]. Ann Rheum Dis. 2009 Jan;68(1):57–62. PubMed PMID: 18292102; eng
  • Mori S, Hirose J, Yonemura K. Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to development of resistance to disease-modifying antirheumatic drugs in early rheumatoid arthritis. Clin Rheumatol. 2010 Dec;29(12):1357–1366. PubMed PMID: 20383728; eng.
  • Gossec L, Dougados M, Goupille P, et al. Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study. Ann Rheum Dis. 2004 Jun;63(6):675–680. PubMed PMID: 15140774; PubMed Central PMCID: PMCPMC1755028.
  • Reuther LO, Vainer B, Sonne J, et al. Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine-tolerant and -intolerant patients with various disorders. The impact of TPMT genotyping in predicting toxicity [Multicenter Study]. Eur J Clin Pharmacol. 2004 Jan;59(11):797–801. PubMed PMID: 14634700; eng
  • Lee YH, Song GG. Associations between the C677T and A1298C polymorphisms of MTHFR and the efficacy and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis [Research Support, Non-U.S. Gov’t Review]. Clin Drug Investig. 2010;30(2):101–108. PubMed PMID: 20067328; eng.
  • Owen SA, Lunt M, Bowes J, et al. MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms [Meta-Analysis Research Support, Non-U.S. Gov’t]. Pharmacogenomics J. 2013 Apr;13(2):137–147. PubMed PMID: 21931346; eng.
  • Qiu Q, Huang J, Shu X, et al. Polymorphisms and pharmacogenomics for the clinical efficacy of methotrexate in patients with rheumatoid arthritis: a Systematic Review and Meta-analysis. Sci Rep. 2017 Mar 7;7:44015. PubMed PMID: 28266606; PubMed Central PMCID: PMC5339794. eng.
  • Blom HJ, Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis. 2011 Feb;34(1):75–81. PubMed PMID: 20814827; PubMed Central PMCID: PMC3026708. eng.
  • Weisman MH, Furst DE, Park GS, et al. Risk genotypes in folate-dependent enzymes and their association with methotrexate-related side effects in rheumatoid arthritis. Arthritis Rheum. 2006 Feb;54(2):607–612. PubMed PMID: 16447238; eng.
  • Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995 May;10(1):111–113. PubMed PMID: 7647779; eng.
  • Johnson TB, Nair MG, Galivan J. Role of folylpolyglutamate synthetase in the regulation of methotrexate polyglutamate formation in H35 hepatoma cells. Cancer Res. 1988 May 1;48(9):2426–2431. PubMed PMID: 2451560; eng
  • Dervieux T, Furst D, Lein DO, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004 Sep;50(9):2766–2774. PubMed PMID: 15457444; eng.
  • Dervieux T, Kremer J, Lein DO, et al. Contribution of common polymorphisms in reduced folate carrier and gamma-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis. Pharmacogenetics. 2004 Nov;14(11):733–739. PubMed PMID: 15564880; eng.
  • Dervieux T, Greenstein N, Kremer J. Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum. 2006 Oct;54(10):3095–3103. PubMed PMID: 17009228; eng
  • Drozdzik M, Rudas T, Pawlik A, et al. Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis. Pharmacogenomics J. 2007 Dec;7(6):404–407. PubMed PMID: 17325736; eng.
  • James HM, Gillis D, Hissaria P, et al. Common polymorphisms in the folate pathway predict efficacy of combination regimens containing methotrexate and sulfasalazine in early rheumatoid arthritis. J Rheumatol. 2008 Apr;35(4):562–571. PubMed PMID: 18322994; eng.
  • Lee YC, Cui J, Costenbader KH, et al. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Rheumatology (Oxford, England). 2009 Jun;48(6):613–617. PubMed PMID: 19193698; PubMed Central PMCID: PMC2681284. eng.
  • Sharma S, Das M, Kumar A, et al. Interaction of genes from influx-metabolism-efflux pathway and their influence on methotrexate efficacy in rheumatoid arthritis patients among Indians. Pharmacogenet Genomics. 2008 Dec;18(12):1041–1049. PubMed PMID: 19093297; eng.
  • Stamp LK, Chapman PT, O’Donnell JL, et al. Polymorphisms within the folate pathway predict folate concentrations but are not associated with disease activity in rheumatoid arthritis patients on methotrexate [Research Support, Non-U.S. Gov’t]. Pharmacogenet Genomics. 2010 Jun;20(6):367–376. PubMed PMID: 20386493; eng.
  • Li X, Hu M, Li W, et al. The association between reduced folate carrier-1 gene 80G/A polymorphism and methotrexate efficacy or methotrexate related-toxicity in rheumatoid arthritis: a meta-analysis. Int Immunopharmacol. 2016 Sep;38:8–15. PubMed PMID: 27233001; eng.
  • Dervieux T, Wessels JA, Kremer JM, et al. Patterns of interaction between genetic and nongenetic attributes and methotrexate efficacy in rheumatoid arthritis. Pharmacogenet Genomics. 2012 Jan;22(1):1–9. PubMed PMID: 22044941; eng.
  • Dervieux T, Wessels JA, van der Straaten T, et al. Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate efficacy and tolerability in rheumatoid arthritis. Pharmacogenet Genomics. 2009 Dec;19(12):935–944. PubMed PMID: 19858780; eng.
  • Senapati S, Singh S, Das M, et al. Genome-wide analysis of methotrexate pharmacogenomics in rheumatoid arthritis shows multiple novel risk variants and leads for TYMS regulation. Pharmacogenet Genomics. 2014 Apr;24(4):211–219. PubMed PMID: 24583629; eng.
  • Taylor JC, Bongartz T, Massey J, et al. Genome-wide asociation study of response to methotrexate in early rheumatoid arthritis patients. Pharmacogenomics J. 2018; Forthcoming.
  • Cobb J, Cule E, Moncrieffe H, et al. Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases. Pharmacogenomics J. 2014 Aug;14(4):356–364. PubMed PMID: 24709693; PubMed Central PMCID: PMCPMC4091986.
  • Daly AK, Day CP. Candidate gene case-control association studies: advantages and potential pitfalls. Br J Clin Pharmacol. 2001 Nov;52(5):489–499. PubMed PMID: 11736857; PubMed Central PMCID: PMC2014606. eng
  • Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604–10609. PubMed PMID: 16009939; PubMed Central PMCID: PMCPMC1174919.
  • Plant D, Wilson AG, Barton A. Genetic and epigenetic predictors of responsiveness to treatment in RA. Nat Rev Rheumatol. 2014 Jun;10(6):329–337. PubMed PMID: 24535543.
  • Kim YI, Logan JW, Mason JB, et al. DNA hypomethylation in inflammatory arthritis: reversal with methotrexate. J Lab Clin Med. 1996 Aug;128(2):165–172. PubMed PMID: 8765212
  • Karouzakis E, Gay RE, Michel BA, et al. DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum. 2009 Dec;60(12):3613–3622. PubMed PMID: 19950268.
  • de Andres MC, Perez-Pampin E, Calaza M, et al. Assessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate. Arthritis Res Ther. 2015 Aug;29(17):233. PubMed PMID: 26330155; PubMed Central PMCID: PMCPMC4556005.
  • Cribbs AP, Kennedy A, Penn H, et al. Treg cell function in rheumatoid arthritis is compromised by ctla-4 promoter methylation resulting in a failure to activate the indoleamine 2,3-dioxygenase pathway. Arthritis & Rheumatology (Hoboken, NJ). 2014 Sep;66(9):2344–2354. PubMed PMID: 24891289.
  • Cribbs AP, Kennedy A, Penn H, et al. Methotrexate restores regulatory t cell function through demethylation of the foxp3 upstream enhancer in patients with rheumatoid arthritis. Arthritis & Rheumatology (Hoboken, NJ). 2015 May;67(5):1182–1192. PubMed PMID: 25604080.
  • Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 1999 Nov;29(11):1181–1189. PubMed PMID: 10598751.
  • Murota A, Suzuki K, Kassai Y, et al. Serum proteomic analysis identifies interleukin 16 as a biomarker for clinical response during early treatment of rheumatoid arthritis. Cytokine. 2016 Feb;78:87–93. PubMed PMID: 26700586.
  • Obry A, Lequerre T, Hardouin J, et al. Identification of S100A9 as biomarker of responsiveness to the methotrexate/etanercept combination in rheumatoid arthritis using a proteomic approach. PLoS One. 2014;9(12):e115800. . PubMed PMID: 25546405; PubMed Central PMCID: PMCPMC4278766
  • Drynda S, Ringel B, Kekow M, et al. Proteome analysis reveals disease-associated marker proteins to differentiate RA patients from other inflammatory joint diseases with the potential to monitor anti-TNFalpha therapy. Pathol Res Pract. 2004;200(2):165–171. PubMed PMID: 15237925
  • Smith SL, Plant D, Eyre S, et al. The predictive value of serum S100A9 and response to etanercept is not confirmed in a large UK rheumatoid arthritis cohort. Rheumatology (Oxford, England). 2017 Jun 1;56(6):1019–1024. PubMed PMID: 28096457; PubMed Central PMCID: PMCPMC5445600.
  • Gindzienska-Sieskiewicz E, Radziejewska I, Domyslawska I, et al. Changes of glycosylation of IgG in rheumatoid arthritis patients treated with methotrexate. Adv Med Sci. 2016 Sep;61(2):193–197. PubMed PMID: 26876088.
  • Lundstrom SL, Hensvold AH, Rutishauser D, et al. IgG Fc galactosylation predicts response to methotrexate in early rheumatoid arthritis. Arthritis Res Ther. 2017 Aug 9;19(1):182. PubMed PMID: 28793911; PubMed Central PMCID: PMCPMC5549282.
  • Chimenti MS, Tucci P, Candi E, et al. Metabolic profiling of human CD4+ cells following treatment with methotrexate and anti-TNF-alpha infliximab. Cell Cycle. 2013 Sep 15;12(18):3025–3036. PubMed PMID: 23974102; PubMed Central PMCID: PMCPMC3875677.
  • Monti S, Montecucco C, Bugatti S, et al. Rheumatoid arthritis treatment: the earlier the better to prevent joint damage. RMD Open. 2015;1(Suppl1):e000057. PubMed PMID: 26557378; PubMed Central PMCID: PMCPMC4632152.
  • Nielen MM, Van Schaardenburg D, Reesink HW, et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004 Feb;50(2):380–386. PubMed PMID: 14872479.
  • Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2010 Sep;69(9):1580–1588. PubMed PMID: 20699241.
  • Wessels JA, Van Der Kooij SM, Le Cessie S, et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis. Arthritis Rheum. 2007 Jun;56(6):1765–1775. PubMed PMID: 17530705; eng.
  • Alex P, Szodoray P, Knowlton N, et al. Multiplex serum cytokine monitoring as a prognostic tool in rheumatoid arthritis. Clin Exp Rheumatol. 2007 Jul-Aug;25(4):584–592. PubMed PMID: 17888215.
  • Barra L, Bykerk V, Pope JE, et al. Anticitrullinated protein antibodies and rheumatoid factor fluctuate in early inflammatory arthritis and do not predict clinical outcomes. J Rheumatol. 2013 Aug;40(8):1259–1267. PubMed PMID: 23378461.
  • Ally MM, Hodkinson B, Meyer PW, et al. Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. BMC Musculoskelet Disord. 2015 May;29(16):130. PubMed PMID: 26021985; PubMed Central PMCID: PMCPMC4446850.
  • Fransen J, Kooloos WM, Wessels JA, et al. Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure. Pharmacogenomics. 2012 Jul;13(9):1087–1094. PubMed PMID: 22838954.
  • Jenko B, Tomsic M, Jekic B, et al. Clinical pharmacogenetic models of treatment response to methotrexate monotherapy in slovenian and serbian rheumatoid arthritis patients: differences in patient’s management may preclude generalization of the models. Front Pharmacol. 2018;9:20. PubMed PMID: 29422864; PubMed Central PMCID: PMCPMC5788961.
  • Brzustewicz E, Henc I, Daca A, et al. Autoantibodies, C-reactive protein, erythrocyte sedimentation rate and serum cytokine profiling in monitoring of early treatment. Cent Eur J Immunol. 2017;42(3):259–268. . PubMed PMID: 29204090; PubMed Central PMCID: PMCPMC5708207
  • Gerards AH, de Lathouder S, de Groot ER, et al. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatology (Oxford, England). 2003 Oct;42(10):1189–1196. PubMed PMID: 12777636.
  • Haroon N, Srivastava R, Misra R, et al. A novel predictor of clinical response to methotrexate in patients with rheumatoid arthritis: a pilot study of in vitro T cell cytokine suppression. J Rheumatol. 2008 Jun;35(6):975–978. PubMed PMID: 18464312
  • Etzerodt A, Maniecki MB, Moller K, et al. Tumor necrosis factor alpha-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163. J Leukoc Biol. 2010 Dec;88(6):1201–1205. PubMed PMID: 20807704.
  • Greisen SR, Moller HJ, Stengaard-Pedersen K, et al. Macrophage activity assessed by soluble CD163 in early rheumatoid arthritis: association with disease activity but different response patterns to synthetic and biologic DMARDs. Clin Exp Rheumatol. 2015 Jul-Aug;33(4):498–502. PubMed PMID: 25962601.
  • Peres RS, Liew FY, Talbot J, et al. Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2509–2514. PubMed PMID: 25675517; PubMed Central PMCID: PMCPMC4345589.
  • Chara L, Sanchez-Atrio A, Perez A, et al. The number of circulating monocytes as biomarkers of the clinical response to methotrexate in untreated patients with rheumatoid arthritis. J Transl Med. 2015 Jan;16(13):2. PubMed PMID: 25592233; PubMed Central PMCID: PMCPMC4310181.
  • Seitz M, Zwicker M, Villiger PM. Pretreatment cytokine profiles of peripheral blood mononuclear cells and serum from patients with rheumatoid arthritis in different american college of rheumatology response groups to methotrexate. J Rheumatol. 2003 Jan;30(1):28–35. PubMed PMID: 12508386
  • Sugiyama D, Nishimura K, Tamaki K, et al. Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2010 Jan;69(1):70–81. PubMed PMID: 19174392; eng.
  • Saevarsdottir S, Wedren S, Seddighzadeh M, et al. Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the epidemiological investigation of rheumatoid arthritis and the swedish rheumatology register cohorts. Arthritis Rheum. 2011 Jan;63(1):26–36. PubMed PMID: 20862678; eng.
  • Saevarsdottir S, Wallin H, Seddighzadeh M, et al. Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial. Ann Rheum Dis. 2011 Mar;70(3):469–475. PubMed PMID: 21149498; eng.
  • Drouin J, Haraoui B, E Initiative G. Predictors of clinical response and radiographic progression in patients with rheumatoid arthritis treated with methotrexate monotherapy. J Rheumatol. 2010 Jul;37(7):1405–1410. PubMed PMID: 20436076; eng.
  • Stamp LK, O’Donnell JL, Chapman PT, et al. Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving long-term methotrexate treatment. Arthritis Rheum. 2009 Aug;60(8):2248–2256. PubMed PMID: 19644853; eng.
  • Joseph RM, Movahedi M, Dixon WG, et al. Smoking-related mortality in patients with early rheumatoid arthritis: a retrospective cohort study using the clinical practice research datalink. Arthritis Care Res (Hoboken). 2016 Nov;68(11):1598–1606. PubMed PMID: 26990778; PubMed Central PMCID: PMC5091627. eng.
  • Emery P. Evidence supporting the benefit of early intervention in rheumatoid arthritis. J Rheumatology Suppl. 2002 Nov;66:3–8. PubMed PMID: 12435162; eng.
  • Smolen JS, Landewe R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017 Jun;76(6):960–977. PubMed PMID: 28264816; eng.
  • Singh JA, Saag KG, Bridges SL Jr., et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis & Rheumatology (Hoboken, NJ). 2016 Jan;68(1):1–26. PubMed PMID: 26545940; eng.
  • Mottonen T, Hannonen P, Korpela M, et al. Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum. 2002 Apr;46(4):894–898. PubMed PMID: 11953964; eng.
  • Anderson JJ, Wells G, Verhoeven AC, et al. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum. 2000 Jan;43(1):22–29. PubMed PMID: 10643696; eng.
  • Maradit-Kremers H, Nicola PJ, Crowson CS, et al. Patient, disease, and therapy-related factors that influence discontinuation of disease-modifying antirheumatic drugs: a population-based incidence cohort of patients with rheumatoid arthritis. J Rheumatol. 2006 Feb;33(2):248–255. PubMed PMID: 16358365; eng
  • Korell J, Duffull SB, Dalrymple JM, et al. Comparison of intracellular methotrexate kinetics in red blood cells with the kinetics in other cell types. Br J Clin Pharmacol. 2014 Mar;77(3):493–497. PubMed PMID: 23844933; PubMed Central PMCID: PMC3952723. eng.
  • Hope HF, Bluett J, Barton A, et al. Psychological factors predict adherence to methotrexate in rheumatoid arthritis; findings from a systematic review of rates, predictors and associations with patient-reported and clinical outcomes. RMD Open. 2016;2(1):e000171. PubMed PMID: 26848403; PubMed Central PMCID: PMC4731843. eng.
  • Smolen JS, Aletaha D. Forget personalised medicine and focus on abating disease activity. Ann Rheum Dis. 2013 Jan;72(1):3–6. PubMed PMID: 23136241.
  • Gwinnutt JM, Symmons DPM, MacGregor AJ, et al. Twenty-year outcome and association between early treatment and mortality and disability in an inception cohort of patients with rheumatoid arthritis: results from the norfolk arthritis register. Arthritis & Rheumatology (Hoboken, NJ). 2017 Aug;69(8):1566–1575. PubMed PMID: 28425173; PubMed Central PMCID: PMCPMC5600136.
  • Barton A, Pitzalis C. Stratified medicine in rheumatoid arthritis-the MATURA programme. Rheumatology (Oxford, England). 2017 Aug 1;56(8):1247–1250. PubMed PMID: 28165532.
  • [cited 2018 Feb 28]. Available from: https://www.sheffield.ac.uk/FRAX/

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.